A number of pharmaceutical agents have been developed for use as antioxidants and anti-inflammatory agents. These pharmaceutical agents, particularly anti-inflammatory agents, have adverse actions such as drowsiness, gastrointestinal troubles, and their continuous administration for a long period cause a problem. Because of these adverse reactions, there is a strong demand for antioxidant and anti-inflammatory pharmaceutical agents derived from natural products which can be administered long term, are safe, and cause no adverse reactions.
Tea (Camellia sinensis (L.) Kuntze) is one of the most popular beverages in the world. Tea leaf is known to be rich in flavonoids, including catechins, and their derivaties which are polyphenols (a compound consisting of one aromatic ring which contains at least one hydroxyl group is classified as a simple phenol. A polyphenol therefore consists of more than one aromatic ring, and more than two hydroxyl groups).
Many studies have demonstrated that green tea and black tea polyphenols have anti-inflammatory, anti-cancer, and anti-cardiovascular disease activity (Vinson, 2000, Biofactors 13: 127-132; Weisburger et al., 2002, Food & Chemical Toxicology, 40:1145-1154.). These biological activities are believed to be due to their antioxidant activity through scavenging reactive oxygen species (ROS) and free radicals. Theaflavins have been regarded as one of the important biologically active components in black tea and the green tea catechins are of similar importance. Indeed, there are a number of reports disclosing the biological activities of theaflavins as a mixture. However, even though tea is consumed daily and in large quantities throughout the world, limited information is available concerning biological activity of individual tea components or their use as pharmaceutical agents.
There are a number of prior art references, which disclose compounds having chemical structural formulas to some of those disclosed in the present invention (Coxon et al., 1970, Tetrahedron Letters, 60: 5241-5246; Leung et al., 2001, The Journal of Nutrition, 2248-2251; Lewis et al., 1998, Phytochemistry, 49: 2511-2519; Lin et al., 1999, European Journal of Pharmacology, 376: 379-388; Miller et al., 1996, FEBS Letters, 392: 40-44; Obanda et al., 2001, Food Chemistry, 75: 395-404; Shiraki et al., 1994, Mutat. Res., 323: 29-34; Tanaka et al., 2001, J. Agric. Food Chem, 49: 5785-5789; Tanaka et al., 2002, J. Agric. Food Chem, 50: 2142-2148; Wan et. al., 1997, J. Sci. Food Agric., 74: 401-408; Wiseman et al., 1997, Critical Reviews in Food Science and Nutrition, 37: 705-718; Yang et al., 1997, Carcinogenesis, 18: 2361-2365). These prior art references disclose the chemistry of polyphenolic compounds isolated from tea. Some of these compounds contain benzotropolone moiety.
The present inventors have sought to discover pharmaceutical preparations having antioxidant and anti-inflammatory activity, and to identify essential agent(s) for treating inflammatory conditions. The present inventors have found that the compounds of the present invention having benzotropolone as a common moiety possess anti-inflammatory activity and that the compounds of the present invention can be prepared by employing simple and unique methods of synthesis.